The present invention relates to the field of membrane transport, particularly to the control over membrane transport of one species by another, and, more particularly, to the control of transport through a membrane covering a sensing element.
Transduction of a physical stimulus into a current or a voltage that may be read by standard electronic circuits is an essential component of measurement science. A device that responds in a quantitative fashion to the presence of a particular chemical species, or a class of chemical species, is known as a sensor. Sensors respond to chemical species dispersed throughout liquid, in particular aqueous, or gaseous media. The preferred requirements for sensors are several: they respond rapidly, and with high sensitivity and selectivity. Sensors are also preferably stable, yield reproducible, reversible response, are relatively easy to calibrate, and are compact.
Since most species to be measured by sensors are mixed with many other species, there is a need for sensors to be selective. Selectivity is an enhanced response for one particular species, or class of species, in the presence of others. Sensors often comprise a measuring element, such as an electrode, covered with a material designed to impart selective transport of a chemical species to be detected. For example, yttrium-doped zirconia, an oxide ion conducting material (see Schwank and DiBattista, Materials Research Society Bulletin, 24, 44 (1999)), is widely used in the automotive industry to sense oxygen concentration in engines.
Sensors in contact with gases or liquids, water in particular, frequently rely on a polymeric membrane coating for providing selectivity. The membrane may be designed to allow selective passage of a species across the membrane to a responsive element behind the membrane. For example, Prohaska et al. (U.S. Pat. No. 6,682,638) disclose a miniaturized sensor comprising a polymer ionomer coating an electrode for detecting species in the gas or vapor phase. The Clark oxygen electrode (see Sawyer et al. Electrochemistry for Chemists, 2nd ed, Wiley, New York, 1995) comprises a semipermeable fluoropolymer membrane across which oxygen, dissolved in solution, can diffuse and initiate an electrochemical reaction at a platinum electrode. Electrodes selective for ions may be constructed by immobilizing an ion exchanger within a polymer membrane, or a thin film liquid sandwiched between two polymeric membranes. A comprehensive list of such electrodes described up to 1990 can be found in Umezawa, Handbook of Ion-Selective Electrodes: Selectivity Coefficients; CRC Press: Boca Raton, Ann Arbor, Boston, 1990. The membranes are typically based on a polymer such as polyvinyl chloride (PVC) or a polyurethane and usually also contain a water immiscible organic liquid which has plasticizer properties.
Alternatively, the surface of the membrane is modified to permit selective interaction with a chemical species, or a class of chemical species.
Membranes formed by casting, dip coating, spraying or other means mainly rely on nonspecific interactions, such as van der Waals, crystal packing interactions, and insolubility in water. For example, a membrane of PVC may be formed over an electrode by casting or dip coating. PVC, being insoluble in water, remains intact in contact with aqueous solutions. Membranes made from materials that tend to be less mechanically stable in contact with their sensing media are often stabilized by the introduction of chemical crosslinking. These crosslinks are introduced, during the deposition, or post-deposition, by irreversible chemical reactions.
Recently, membranes comprising two or more component polymeric materials (including biomacromolecules) that are held together by interactions of a more determinate nature have been described. These membranes are prepared using at least two component polymeric materials which are alternately deposited on a substrate or substratum. Each deposition deposits a layer of material, and the membrane is thus often termed a “multilayer.” See Decher and Schlenoff, Eds., Multilayer Thin Films—Sequential Assembly of Nanocomposite Materials, Wiley-VCH, Weinheim (2003); Decher, Science, 277, 1232 (1997). The component polymeric materials interact at specific points along the polymeric molecules. These interactions are reversible, and the membranes, or thin films that are made are therefore termed Multiple Reversible Interaction Point Membranes, MRIPMs. Reversible interaction types employed for MRIPMs include electrostatic or ion pairing interactions, hydrogen bonding, base pairing in nucleic acids, polar acid-base interactions, charge transfer interactions and hydrophobic interactions. Combinations of these interactions have also been employed for making MRIPMs. Interactions between interaction points on component polymeric materials effectively form a plurality of physical crosslink points, which act cooperatively to hold the membrane together.
Preferred interactions are electrostatic, or ion pairing, interactions between polyelectrolytes. Polyelectrolytes are macromolecules comprising a plurality of charged repeat units. Amorphous complexes may be formed by contacting solutions of polyelectrolytes bearing opposite charges (see Dautzenberg et al. Polyelectrolytes. Formation, Characterization and Application, Hanser, Munich, 1994). The driving force for association, or complexation, of polyelectrolytes is multiple ion pairing between oppositely charged repeat units on different molecules. These same driving forces are employed for preparing membranes, or thin films, of polyelectrolyte complex. Decher and Hong (U.S. Pat. No. 5,208,111) disclose a method for a buildup of multilayers by alternating dipping, i.e., cycling a substrate between two reservoirs containing aqueous solutions of polyelectrolytes of opposite charge, with an optional rinse step in polymer-free solution following each immersion. Each cycle adds a layer of polymer via ion pairing forces to the oppositely-charged surface and reverses the surface charge thereby priming the film for the addition of the next layer. Films prepared in this manner tend to be uniform, follow the contours and irregularities of the substrate, and are typically between about 10 nm and about 10,000 nm thick. The thickness of a film depends on many factors, including the number of layers deposited, the ionic strength of the solutions, the types of polymers, the deposition time, the solution pH, the temperature, and the solvent used. Although studies have shown that substantial interpenetration of the individual polymer layers results in little composition variation over the thickness of a film, such polymer thin films are, nevertheless, referred to as polyelectrolyte multilayers (PEMUs). PEMUs are a subset of MRIPMs.
Though recently developed, PEMUs are being used in a wide variety of fields including light emitting devices, nonlinear optics, sensors, enzyme active thin films, electrochromics, conductive coatings, patterning, anticorrosion coatings, antistatic coatings, lubricating films, biocompatibilization, dialysis, and as selective membranes for the separation of gaseous and dissolved ionic species. See Fou et al., J. Appl. Phys., 79, 7501 (1996); Decher et al., J. Biosens. Bioelect. 9, 677 (1994); Sun et al., Macromol. Chem. Phys. 197, 147 (1996); Onda et al., Biotech Bioeng. 51, 163 (1996); Lvov et al., J. Am. Chem. Soc. 120, 40733 (1998); Laurent et al., Langmuir 13, 1552 (1997); Stepp et al., J. Electrochem. Soc. 144, L155 (1997); Cheung et al., Thin Solid Films 244, 985 (1994); Hammond et al., Macromolecules 28, 7569 (1995); Huck et al., Langmuir 15, 6862 (1999); Stroeve et al., Thin Solid Films 284, 708 (1996); Levasalmi et al., Macromolecules 30, 1752 (1997); Harris et al., Langmuir 16, 2006 (2000); Krasemann et al., Langmuir 16, 287 (2000); Harris et al., J. Am. Chem. Soc. 121, 1978 (1999); Harris et al., Chem. Mater. 12, 1941 (2000).
Polyelectrolyte complexes are known to moderate interactions with biological systems, usually with the purpose of rendering an article or object inert to biological activity. That is, a coating of polyelectrolyte complex does not elicit undesirable inflammation or immune responses. Fine tuning of protein adsorption at the solid/liquid interface is critical in certain areas of materials science and biomedical engineering. Systems for delivery or biosensors, for example, bear modified surfaces designed to enhance or minimize protein adsorption. The latter goal is generally desirable for blood-contacting devices, chromatographic supports, contact lenses, and immunoassays, to name a few. Due to their ease of use and water compatibility, PEMUs have been investigated as surface-modifying agents for protein interactions (see Ladam, G.; Gergely, C.; Senger, B.; Decher, G.; Voegel, J. C.; Schaaf, P.; Cuisinier, F. J. G. Biomacromolecules 1, 674 (2000)). For example, polyelectrolyte complexes have been coated on Islets of Langerhans, an insulin-producing biological apparatus, to make them more acceptable when implanted in vivo (see O'Shea and Sun, Diabetes 35, 953 (1986) and Goosen et al. U.S. Pat. No. 4,673,566 (1987)). In another example, an ocular contact lens treated with a polyelectrolyte complex improves the properties of the lens (see Ellis and Salamone, U.S. Pat. No. 4,168,112 (1979)). Winterton et al. (U.S. Pat. No. 6,451,871 (2002)) disclose a method of making polyelectrolyte complexes on the surface of a contact lens by the multilayering method.
The rate of transport of species across MRIPMs, when they are used as sensors, and for other applications, is determined by a variety of factors. For PEMUs, one of these factors is whether there are sites available within the membrane to accommodate a particular species that is traversing the membrane. Creation of sites for transport within PEMUs has been termed “doping” and has been accomplished by the addition of salt (NaCl). See Farhat and Schlenoff, Langmuir, 17, 1184 (2001).
Coordinated experimental and theoretical studies have been carried out to ascertain how ion transport though polyelectrolyte complex is reversibly regulated by solution ionic strength (see Farhat and Schlenoff, J. Am. Chem. Soc., 125, 4627 (2003)). In the presence of external salt species (such as NaCl), ions are forced into the soft material, which becomes an ion exchanger/transporter. For n Pol+Pol− polyelectrolyte ion pairs, this reversible process is represented by:nPol+Pol−+nyNa++nyCl−→(1−y)nPol+Pol−+nyPol+Cl−+nyPol−Na+  Eq. 1where y is the doping level, or the fraction of Pol+Pol− pairs converted to Pol+Cl− and Pol−Na+ transporting sites. The driving force for doping is reversible chemical potential, controlled directly by concentration. The doping reaction summarized by this equation creates randomly distributed clusters of sites—“defects” among which ions may hop. Transport is favored for ions of lower charge and the diffusion rate is a strong nonlinear function of doping level—both Monte Carlo and continuum probability theoretical approaches predict this trend.
Electrogenerated chemiluminescence, ECL, also known as electroluminescence, is a technique whereby a species is oxidized or reduced at an electrode to yield a product that is in an excited, or high-energy state. During relaxation of this excited state, light is generated, which may be detected by a light sensitive instrument, such as a photomultiplier, photodiode, photodiode array, or charged coupled device. Often, additional reagents are required to promote more efficient emission of light. Several reviews on the topic are available (see Faulkner and Bard, Electroanalytical Chemistry 10, 1, 1977). See also U.S. Pat. Nos. 5,068,088, 5,093,268, 5,061,445, 5,238,808, 5,147,806, 5,247,243, 5,296,191, 5,310,687, 5,221,605.
Many ECL systems comprise modified electrodes. For example, Dixon et al. (U.S. Pat. No. 5,075,172) disclose an electroluminescent layer comprising a charged fluorinated polymer coating an electrode, which traps an electroluminescent species. Zhang and Bard (U.S. Pat. No. 5,324,457) disclose an electrode coated with a nonpolymeric layer of electroluminescent material. The use of ECL in assays is reviewed in detail by, for example, Knight et al., Analyst, 119, 879 (1994).